A lesion or wound can be obtained either by external damage, giving a traumatic wound emanating from an accident or a surgical operation, or by a pathological process in the tissue. An ulcer, such as peptic and bone ulcer, mainly refers to a wound in the skin or membranes. Lesions also comprises damages in varying other tissues, such as bone fractures. In this description the expression wound is used for all types of damages of the human or animal body. Wounds can be classified as an acute or a chronic wound.
The mechanisms involved in wound healing can generally be divided into four phases, that is hemostasis, inflammation, proliferation and maturation. During the inflammation leucocytes are accumulated in order to combat bacteria and the permeability of the walls of the vessels is increased leading to swelling. Many of said substances also promotes an improved microcirculation leading to redness and heat. If an infection is not developed the number of leucocytes will be reduced and replaced by monocytes that is macrophages and lymphocytes releasing i.e. growth factors (cytokines) as well as a number of chemical substances, such as histamine, serotonin, prostaglandins, which are the main regulators of the beginning as well as the continuation of the wound healing process. The most important regulating cell is the macrophage. In the proliferation phase connective tissue is formed, new blood vessels are growing in and injured tissue is regenerated. Fibroblasts are the dominating cells after about a week, the inflammation decreases and the strength of the wound is rapidly increased. During the maturation phase, finally, the tissue protein collagen is stabilised and scar tissue is formed. This phase might go on for a long time during which the strength is improved and the regeneration is continued, for instance of nerve tissue. In order to obtain an optimal wound healing the supply of different vitamins and trace elements as well as nutrients should be sufficient as well as the oxygen supply.
Uncompromised cellular homeostasis is essential for wound healing and repair and in the healing tissue certain conditions are required for the development of granulation tissue and epithelial budding. The homeostatic conditions include the degree of hydration, sufficient blood perfusion, availability of various growth factors, an appropriate partial pressure of oxygen, acceptable levels of nonpathogenic microflora and maintenance of voltage gradients between the wound and adjacent normal skin. In a homeostatic environment cells are bathed in body fluids that allow for normal growth and repair processes.
Chronic wounds or indolent, nonhealing wounds may arise from different causes including infection, the presence of foreign bodies or toxic irritants, burns, prolonged cutaneously applied pressure and poor blood supply owing to impaired circulation. In a chronic wound the tissue homeostasis and the wound environment are compromised so that either healing fails to occur or healing begins but is subsequently halted. Factors involved in said conditions are tissue necrosis, dehydration, chronic wound edema, fibrotic induration and small blood vessel disease.
Leg ulcer is one type of chronic wounds which is found in a substantial part of the population, increasing with advancing age. The course of the disease can last from a couple of months up to several decades and will bring about heavy expenses for the society as well as a great suffering for the individual patient. Pressure ulcer, decubitus ulcer, or bedsore is another type of chronic wounds which mainly affects elderly people. Chronic non-healing ulcers are a serious problem in diabetic patients.
In order to provide a homeostatic environment the wound can be covered with an occlusive dressing designed to keep the wound moist. This will however bring about a risk of promoting wound infection.
One of the oldest therapeutic methods used for treating chronic open wounds is hydrotherapy, which today can be performed in a whirlpool bath. By this adherent dressings can be soaked off and necrotic tissue debrided.
In chronic dermal and indolent ulcers cell migration from the wound periphery may not occur if necrotic, desiccated tissue is obstructing it. The necrotic tissue impedes the formation of granulation tissue and prevents epithelial cells from migrating across the wound. Debridement, that is the removal of necrotic tissue from a wound, is therefore necessary not only to remove dead tissue on which bacteria survive to allow the healing processes of granulation development and fibroblastic deposition of collagen upon which the epidermal cells can migrate and close the wound, but also to remove many of the microorganisms that may be present. This debridement can be performed by topical application of enzymes, by facilitating autolysis, that is self-digestion of necrotic tissue by enzymes that are naturally present in wound fluids, with synthetic dressings or by surgical excision. Once debrided a wound will normally undergo granulation, contraction and epithelialization.
There are a number of topical agents which can have a profound effect on the rate of wound healing. Topical antimicrobials and cleansers have frequently been overused in wound therapy resulting in harmful cytotoxic effects and minimal antimicrobial and cleansing effectiveness. As examples of such agents can be mentioned iodophor, sodium hypochlorite solution, hydrogen peroxide and zinc oxide.
It has been hypothesized that impaired wound healing may result from lack of adequate stimulation by growth factors.
In fact growth factors have been used in clinical trials to test if they can improve wound closure in patients with chronic nonhealing wounds. Recently promising animal experiments on wound healing have been performed with growth factors, but a local administration on chronic wounds in humans has not been as successful. It has been suggested to use several different growth factors in combination with a protease inhibitor.
Another approach has been to transplant epithelial cells alone or in combination with fibroblasts and extracellular matrix components. It has also been speculated in the use of genes regulating the synthesis of healing polypeptides in the transplanted cells or applied directly on the wound.